The present invention relates to a non-specific adsorption inhibitor which can be applied to the surface of particles for immunodiagnosis, for example, probe-bonded particles, and methods for producing the same.
In recent years, due to a demand for an increase in the inspection sensitivity for the early detection of diseases, an increase in sensitivity of a diagnostic agent has been an important subject. In order to increase the sensitivity of diagnostic agents using a solid phase such as magnetic particles, a method of using enzyme coloring as a detecting means is being replaced by a method of using fluorescence or chemiluminescence, both of which ensure higher sensitivity. Development of these detection techniques is said to have reached a level in which a one molecule-substance for inspection can be theoretically detected. In practice, however, the sensitivity is still insufficient. In diagnosis in which a specific substance is detected in the presence of biomolecules such as blood serum, coexisting biomolecules, secondary antibodies, luminescence substrates, and the like non-specifically adsorb on a solid phase. As a result, noise increases and interferes with promotion of the sensitivity. Therefore, in order to reduce the risk of a sensitivity reduction due to non-specific adsorption of substances other than the substances which can specifically bond to a solid phase surface used for an immunological reaction in an immunodiagnostic measurement, a biological material such as albumin, casein, or gelatin is usually used as a blocking agent (also referred to as a “non-specific adsorption inhibitor”) to inhibit non-specific adsorption and reduce noise.
However, non-specific adsorption occurs in spite of the use of such a blocking agent. In addition, a biologically-derived blocking agent may have a risk of biological infection such as bovine spongiform encephalopathy (BSE). Therefore, development of a high performance blocking agent by chemosynthesis has been desired.
As a chemically-synthesized blocking agent, a vinyl monomer copolymer which has a polyoxyethylene side chain has been proposed (JP-A-11-287802). The proposed method of preparation of such a copolymer, however, can achieve only poor molecular weight reproducibility. The resulting copolymer product thus exhibits only poor blocking effect reproducibility. A polyoxyethylene having two amino groups in one molecular end used as a blocking agent has been proposed (Japanese Patent No. 3,407,397). This blocking agent, however, exhibits only inadequate mutual action with a solid phase. When added as a blocking agent, a major part remains in an aqueous phase, making the resulting product uneconomical. A block copolymer of a polyoxyethylene and pentaethylenehexamine has been proposed as a blocking agent (JP-A-2006-226982). Production and purification of such a block copolymer are difficult because a polyoxyethylene of which both ends are modified by pentaethylenehexamine is easily produced during synthesis of the copolymer. As a method for producing a block agent similar to the block copolymer of a polyoxyethylene and pentaethylenehexamine, a method of using a polyoxyethylene having an acetal end as an intermediate has been proposed (WO 2005/010529). Production and purification of such a block copolymer are difficult because the method produces a large amount of polyoxyethylene dimers.